Abstract:
:Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was performed to test whether an abbreviated ex vivo protocol using vector-laden, coagulated bone marrow aspirates for gene delivery to cartilage defects may be feasible for clinical application. Ovine autologous bone marrow was transduced with adenoviral vectors containing cDNA for green fluorescent protein or transforming growth factor (TGF)-beta1. The marrow was allowed to clot forming a gene plug and implanted into partial-thickness defects created on the medial condyle. At 6 months, the quality of articular cartilage repair was evaluated using histological, biochemical and biomechanical parameters. Assessment of repair showed that the groups treated with constructs transplantation contained more cartilage-like tissue than untreated controls. Improved cartilage repair was observed in groups treated with unmodified bone marrow plugs and Ad.TGF-beta1-transduced plugs, but the repaired tissue from TGF-treated defects showed significantly higher amounts of collagen II (P<0.001). The results confirmed that the proposed method is fairly straightforward technique for application in clinical settings. Genetically modified bone marrow clots are sufficient to facilitate articular cartilage repair of partial-thickness defects in vivo. Further studies should focus on selection of transgene combinations that promote more natural healing.
journal_name
Gene Therjournal_title
Gene therapyauthors
Ivkovic A,Pascher A,Hudetz D,Maticic D,Jelic M,Dickinson S,Loparic M,Haspl M,Windhager R,Pecina Mdoi
10.1038/gt.2010.16subject
Has Abstractpub_date
2010-06-01 00:00:00pages
779-89issue
6eissn
0969-7128issn
1476-5462pii
gt201016journal_volume
17pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::The development of lentiviral vectors that use Rev-independent mechanisms of nuclear export for their genomic RNA could facilitate the construction of novel anti-HIV vectors. We have improved the titers of Rev-independent lentiviral vectors having the SRV-1 CTE by mutating the major splice donor and acceptor sites pre...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301262
更新日期:2000-08-01 00:00:00
abstract::Hydrodynamic gene delivery is an attractive option for non-viral liver gene therapy, but requires evaluation of efficacy, safety and clinically applicable techniques in large animal models. We have evaluated retrograde delivery of DNA to the whole liver via the isolated segment of inferior vena cava (IVC) draining the...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303079
更新日期:2008-03-01 00:00:00
abstract::Various methods for determining the expression of the beta-galactosidase (beta-gal) gene after retroviral transduction were compared as a means to assess retroviral titre. To allow better comparison, different retroviral vectors were constructed carrying two mutants of the green fluorescent protein and assessed as sen...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300519
更新日期:1997-11-01 00:00:00
abstract::The role of gap junctional intercellular communication (GJIC) in bystander killing with herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) was evaluated in U251 cells expressing a dominant-negative connexin 43 cDNA (DN14), and in HeLa cells, reportedly devoid of connexin protein. These cell lines bot...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302487
更新日期:2005-07-01 00:00:00
abstract::We investigated the efficiency of activated polyamidoamine dendrimers, a new class of nonviral vectors, to transfect rabbit and human corneas in ex vivo culture. In addition to assessing the expression of a marker gene we have demonstrated that this approach can be used to induce the production of TNF receptor fusion ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300886
更新日期:1999-05-01 00:00:00
abstract::The efficiency of plasmid gene transfer to skeletal muscle can be significantly improved by the application of an electrical field to the muscle following injection of plasmid DNA. However, this electrotransfer is associated with significant muscle damage which may result in substantial loss of transfected muscle fibr...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301522
更新日期:2001-08-01 00:00:00
abstract::Choroidal neovascularization (CNV) leads to loss of vision in age-related macular degeneration (AMD), the leading cause of blindness in adult population over 50 years old. In this study, we developed intravenously administered, nanoparticulate, targeted nonviral retinal gene delivery systems for the management of CNV....
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.185
更新日期:2009-05-01 00:00:00
abstract::The successful development of adenovirus vectors for vaccines and gene therapy will require a better understanding of the host immune response. Using the ELISPOT assay to measure IFN-gamma-secreting CD8(+) cells, we identify immunodominant epitopes of the adenovirus hexon and DNA-binding protein in BALB/c and C57BL/6 ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302232
更新日期:2004-05-01 00:00:00
abstract::By-pass surgery and percutaneous transluminal (coronary) angioplasty, PT(C)A, are standard techniques for the treatment of vascular occlusions. Their usefulness is limited by by-pass graft failure and restenosis occurring after the procedures. Twenty percent of patients treated with PTCA/PTA need a new revascularizati...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3301866
更新日期:2002-11-01 00:00:00
abstract::Hydrodynamic gene delivery to the liver is an attractive approach for clinical liver gene therapy, but critical aspects of technique remain uncertain. There has not been to date any report of high levels of hydrodynamic gene delivery to the liver, except in rodents. Regional hydrodynamic delivery to individual lobes/s...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.167
更新日期:2010-04-01 00:00:00
abstract::The failure of pharmacological approaches to cure infection with the human immunodeficiency virus (HIV) has renewed the interest in gene-based therapies. Among the various strategies that are currently explored, the blockade of HIV entry into susceptible T cells and macrophages promises to be the most powerful interve...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302755
更新日期:2006-07-01 00:00:00
abstract::A stable packaging cell line (Vero/BC-F) constitutively expressing fusion (F) protein of the human parainfluenza virus type 2 (hPIV2) was established for production of the F-defective and single round-infectious hPIV2 vector in a strategy for recombinant vaccine development. The F gene expression has not evoked cytost...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.55
更新日期:2014-08-01 00:00:00
abstract::The pseudorabies virus (PRV) is a swine alpha herpes virus that is widely used as a neural tracer because of its marked neurotropism and transneuronal transmissibility (Card et al., 1991, 1992; Strack and Loewy 1990). PRV has been used to retrogradely identify spinal cord and brainstem connections to various periphera...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Small interfering RNAs (siRNAs) are emerging as promising therapeutic tools. However, the widespread clinical application of such molecules as modulators of gene expression is still dependent on several aspects that limit their bioavailability. One of the most promising strategies to overcome the barriers faced by gen...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.27
更新日期:2011-07-01 00:00:00
abstract::Adenovirus (Ad) vectors are of utility for many therapeutic applications. Strategies have been developed to alter adenoviral tropism to achieve a cell-specific gene delivery capacity employing fiber modifications allowing genetic incorporation of targeting motifs. In this regard, single chain antibodies (scFv) represe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302603
更新日期:2006-01-01 00:00:00
abstract::Vectors conjugated with ligands recognized by cell surface receptors are of interest for cystic fibrosis gene therapy since these vectors would allow cell-specific targeting. However, an efficient and specific uptake may be abrogated by a subsequent intracellular trafficking leading to an inefficient gene transfer. Th...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301738
更新日期:2002-06-01 00:00:00
abstract::The recent surge of DNA sequence information resulting from the efforts of agencies interested in deciphering the human genetic code has facilitated technological developments that have been critical in the identification of genes associated with numerous disease pathologies. In addition, these efforts have opened the...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301740
更新日期:2002-06-01 00:00:00
abstract::Low levels of expression in haemopoietic cells of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (A Tase), is associated with the dose-limiting sensitivity of these cells to the chemotherapeutic chloroethylating and related methylating agents. Thus, the use of agents which deplete ATase such as O6-benzylg...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::In-stent restenosis results exclusively from neointimal hyperplasia due to mechanical injury and a foreign body response to the prosthesis. Inflammation mediated by monocyte chemoattractant protein-1 (MCP-1) might therefore underlie in-stent restenosis. We recently devised a new strategy for anti-MCP-1 gene therapy by...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302288
更新日期:2004-08-01 00:00:00
abstract::In view of our recent findings that a truncated form of the envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) was efficiently incorporated into MoMLV particles, we studied the generation of Moloney murine leukemia virus (MoMLV)/simian immunodeficiency virus (SIV) pseudotypes. Unlike HIV-1, bot...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300603
更新日期:1998-02-01 00:00:00
abstract::We have comparatively evaluated the efficiency of a series of retroviral vectors transducing the gp91-phox gene, whose defects are responsible for impaired production of superoxide anion (O2-) by phagocytic cells and lead to the X-linked form of chronic granulomatous disease (X-CGD). These vectors included four constr...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301057
更新日期:2000-01-01 00:00:00
abstract::Hepatic fibrosis is a common outcome of chronic liver diseases. In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Recently, it has been shown that gene therapy is an attractive approach for the treatment of he...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301524
更新日期:2001-09-01 00:00:00
abstract::The GM2-gangliosidoses are neurological diseases causing premature death, thus developing effective treatment protocols is urgent. GM2-gangliosidoses result from deficiency of a lysosomal enzyme β-hexosaminidase (Hex) and subsequent accumulation of GM2 gangliosides. Genetic changes in HEXA, encoding the Hex α subunit,...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-019-0120-5
更新日期:2020-05-01 00:00:00
abstract::Excessive activated T-cell proliferation was observed in vivo in one patient after an anti-CD19-chimeric antigen receptor (CAR) T-cell infusion. The patient, who had chemotherapy refractory and CD19+ diffuse large B-cell lymphoma (DLBCL), received an anti-CD19 CAR T-cell infusion following conditioning chemotherapy (f...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-017-0001-8
更新日期:2018-06-01 00:00:00
abstract::Gene transfer vectors encoding two or more genes are potentially powerful research tools and are poised to play an increasingly important role in gene therapy applications. Common strategies employed to express more than one transgene per vector include the use of multiple promoters, internal ribosome entry site (IRES...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303105
更新日期:2008-03-01 00:00:00
abstract::The bystander effect (BSE) is an interesting and important property of the herpes thymidine kinase/ganciclovir (hTK/GCV) system of gene therapy for cancer. With the BSE, not only are the hTK expressing cells killed upon ganciclovir (GCV) exposure but also neighboring wild-type tumor cells. On testing a large number of...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300784
更新日期:1998-12-01 00:00:00
abstract::Catheter-based percutaneous transluminal gene delivery (PTGD) into the coronary artery still falls behind the expectations of an efficient myocardial gene delivery system. In this study gene delivery was applied by selective pressure-regulated retroinfusion through the coronary veins to prolong adhesion of replication...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301079
更新日期:2000-02-01 00:00:00
abstract::More than one hundred different mutations in the gene encoding rhodopsin are associated with a group of retinal degenerations including retinitis pigmentosa, congenital stationary night blindness and retinitis punctata albescens. Given this large heterogeneity of mutations, it would be ideal to develop mutation-indepe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302512
更新日期:2005-08-01 00:00:00
abstract::Gene transfer technology has opened novel treatment avenues toward the treatment of damaged musculoskeletal tissues, and may be particularly beneficial to articular cartilage. There is no natural repair mechanism to heal damaged or diseased cartilage. Existing pharmacologic, surgical and cell based treatments may offe...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302201
更新日期:2004-02-01 00:00:00
abstract::betaTC-tet cells are conditionally immortalized pancreatic beta cells which can confer long-term correction of hyperglycemia when transplanted in syngeneic streptozocin diabetic mice. The use of these cells for control of type I diabetes in humans will require their encapsulation and transplantation in non-native site...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300922
更新日期:1999-06-01 00:00:00